The development of robust methods for facile synthesis of well-defined functional polymers is an ongoing challenge. To circumvent the common incompatibility of reactive side-chain functional groups with polymerization chemistries, there has been considerable effort to develop selective and efficient methods for post-polymerization modification. This is especially true for synthesis of functional polypeptides, which are desirable as mimics of post-translationally modified proteins and for uses in biological and medical applications. Consequently, a variety of precursor polypeptides, and their reactions with functional molecules, have been reported in recent years. Previous efforts have reported the reaction of methionine (Met) residues with alkylating agents as an efficient means to prepare functional polypeptides, which utilizes an inexpensive amino acid precursor and is broad in scope. In those systems, some functional groups can be installed using commercial reagents in water, while others require use of stoichiometric silver salts or preparation of reactive alkyl triflates and anhydrous conditions.
In addition, many of the activating groups in these examples (i.e. carbonyl, alkyne, aryl), also result in the product sulfonium ions that are unstable toward nucleophiles. These unstable sulfonium products often undergo dealkylation. While such reversibility is desirable for temporary modifications, the ability to prepare permanently functionalized materials under mild conditions is also important for many uses.
There exists a need for improved, efficient, general methods of introducing a wide range of functional groups onto polypeptides. Of specific interest are chemoselective reactions that exhibit high yields in protic solvents.